Blood vessel maturation in retinoblastoma tumors: spatial distribution of neovessels and mature vessels and its impact on ocular treatment.
OBJECTIVE
The purposes of this study were to evaluate the spatial distribution of neovessels versus mature vessels in both human retinoblastoma (RB) and LH(BETA)T(AG) tumors, assess similarities and differences between the animal model and the human RB specimens, and determine whether vessel maturation is associated with risk factors for metastasis.


METHODS
Immunohistochemical analyses were performed on human (n = 10) and LH(BETA)T(AG) (n = 11) enucleation specimens to evaluate the spatial distribution of neovessels and mature vessels. In human RB, vessel maturation was correlated with treatment history and metastatic risk factors.


RESULTS
In human RB, the percentage of neovessels was higher in the periphery of the tumor than in the center (P = 0.021). This finding was mostly attributed to the distribution of large-caliber vessels (i.e., neovessels were higher in the periphery for large [P = 0.050]- and medium [P = 0.032]-caliber vessels; and mature vessels were higher in the center for large-caliber vessels [P = 0.032]). In this small series, vessel maturation did not correlate with risk for metastasis. Similar results were observed in LH(BETA)T(AG) tumors. The percentage of large-caliber neovessels was higher in the periphery than in the center (P = 0.038).


CONCLUSIONS
There is a spatially distributed, heterogeneous vessel population containing neovessels and mature vessels in advanced RB disease. There is a significantly higher concentration of mature, large-caliber vessels in the center of tumors that is similar in human RB and LH(BETA)T(AG) retinal tumors. From these data the authors hypothesize that tumor vessel maturation in RB initiates in central regions of the tumor and radiates toward the periphery.
Piña
Yolanda
Y
Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA.
Boutrid
Hinda
H
Schefler
Amy
A
Dubovy
Sander
S
Feuer
William
W
Jockovich
Maria-Elena
ME
Murray
Timothy G
TG
D000199:Actins / Q000378:metabolism; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001808:Blood Vessels / Q000473:pathology; D002675:Child, Preschool; D024141:Collagen Type IV / Q000378:metabolism; D004195:Disease Models, Animal; D000071063:Endoglin; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D019572:Retinal Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D012175:Retinoblastoma / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology
D000199:Actins; D020533:Angiogenesis Inhibitors; D015703:Antigens, CD; D015415:Biomarkers; D024141:Collagen Type IV; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface